Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies
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- 作者：Ana Navarro ; Alberto Boveris ; Manuel J. Bá ; ndez ; Marí ; a Jesú ; s Sá ; nchez-Pino ; Carmen Gó ; mez ; Gerard Muntané ; Isidro Ferrer
- 关键词：Complex I ; mtNOS ; Mn-SOD ; Cytochrome content ; Oxidative damage ; Human brain mitochondria ; Free radicals
- 刊名：Free Radical Biology and Medicine
- 出版年：2009
- 出版时间：15 June 2009
- 年：2009
- 卷：46
- 期：12
- 页码：1574-1580
- 全文大小：415 K
文摘
Frontal cortex samples from frozen human brains were used to assess tissue respiration; content of mitochondria; mitochondrial oxygen uptake; activity of respiratory complexes and of mitochondrial nitric oxide synthase (mtNOS); content of cytochromes a, b, and c; oxidative damage (protein carbonyls and TBARS); and expression of Mn-SOD in patients with Parkinson disease (PD) and with dementia with Lewy bodies (DLB) in comparison with those of normal healthy controls. Brain cortex and mitochondrial O2 uptake and complex I activity were significantly lower in PD and DLB, whereas mtNOS activity, cytochrome content, expression of Mn-SOD, mitochondrial mass, and oxidative damage were significantly higher in the frontal cortex in PD and DLB. The decreases in tissue and mitochondrial O2 uptake and in complex I activity are considered the consequences of mitochondrial oxidative damage. The increases in mtNOS activity and in mitochondrial mass are interpreted as an adaptive response of the frontal cortex that involves increased NO signaling for mitochondrial biogenesis. The adaptive response would partially compensate for mitochondrial dysfunction in these neurodegenerative diseases and would afford a human evolutionary response to shortage of ATP in the frontal cortex.